7-38742254-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014396.4(VPS41):c.2123-133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 817,620 control chromosomes in the GnomAD database, including 22,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5551 hom., cov: 32)
  • Exomes 𝑓: 0.21 (17035 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

Genes affected

VPS41 (HGNC:12713): (VPS41 subunit of HOPS complex) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human ortholog of yeast Vps41 protein which is also conserved in Drosophila, tomato, and Arabidopsis. Expression studies in yeast and human indicate that this protein may be involved in the formation and fusion of transport vesicles from the Golgi. Several transcript variants encoding different isoforms have been described for this gene, however, the full-length nature of not all is known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-38742254-T-C is Benign according to our data. Variant chr7-38742254-T-C is described in ClinVar as [Benign]. Clinvar id is 1273568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.2123-133A>G		intron_variant		ENST00000310301.9
VPS41	NM_080631.4	c.2048-133A>G		intron_variant
VPS41	XM_017011988.2	c.968-133A>G		intron_variant
VPS41	XR_007060008.1	n.2140-133A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.2123-133A>G		intron_variant		1	NM_014396.4	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37618 AN: 152008 Hom.: 5536 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.207 AC: 138013 AN: 665494 Hom.: 17035 AF XY: 0.215 AC XY: 73338 AN XY: 340978

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.248 AC: 37664 AN: 152126 Hom.: 5551 Cov.: 32 AF XY: 0.252 AC XY: 18720 AN XY: 74378

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.227

Alfa AF: 0.212 Hom.: 484

Bravo AF: 0.246

Asia WGS AF: 0.394 AC: 1366 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	17
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11979824; hg19: chr7-38781854;